Malignant gliomas represent a significant class of CNS tumors derived from the glial lineage. Despite recent advances in traditional treatment options, the prognosis for these patients has not changed appreciably. Among the new treatments currently being investigated for malignant cancers, none is as theoretically appealing as immunotherapy because it offers the potential for high tumor-specific toxicity. Immune-based treatments for central nervous system (CNS) gliomas have traditionally lagged behind those of more immunogenic tumors such as melanoma. The relative paucity of defined glioma-associated antigens (GAA) that can be targeted by the immune system may partially account for this situation. Antigens present on melanomas have been extensively characterized, both in humans and murine pre-clinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas, have been shown in humans to share common antigens at the RNA level. However, little is known concerning whether gliomas can be targeted by immune-based strategics that prime T cells to epitopes from melanoma-associated antigens (MAA). The experiments outlined in this proposal are primarily designed to test whether MAA are expressed by gliomas and recognized by the immune system. This proposal will also define the basic immunologic requirements for targeting tumors located within the CNS. The results from this study should not only provide important basic immunologic data concerning T lymphocyte responses in the CNS, but could potentially outline a new immunotherapeutic target for CNS tumors clinically. The tumor immunology program and academic environment at UCLA offers an ideal place to develop as an independent research scientist. World renowned scientists and technology in many disciplines will serve to enhance the ability of Dr. Prins to accomplish the goals set forth in this application. ? ? ? ?
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